(1) An approach using the signal peptides from the glycoproteins of enveloped viruses, either as probes for identifying the receptors and cofactors or as carriers for antivirals, has been tested. Two signal peptides, one from the gp41 envelope protein of human immunodeficiency virus (HIV) and one from the gD protein of herpes simplex virus (HSV), were conjugated to two cargo peptides that permitted detection of cellular entry through inhibition of virus growth, radioactive label, or immunofluorescence. We found that: (a) The signal peptides can penetrate the plasma membranes and carry a cargo with them. (b) The HIV signal peptide conjugates were specific for cells infectable by HIV, whereas the HSV signal peptide conjugates could only enter cells infectable by HSV. And (c) the vero cells, which are not infectable by HIV, when made to express fusin, a newly discovered cofactor for HIV cell fusion, the cell became permeable to HIV signal peptide conjugates, indicating that fusion also mediates gp41 insertion. Thus, our approach provides a means for elucidating the complete mechanism of HIV cell fusion. As a carrier, the peptides also are capable of delivering antivirals into the cell, possibly with improved specificity and, hence, lower cytotoxicity. (2) The complete amino acid sequence of a Mg-dependent, Ca-inhibited phosphatase, purified in this laboratory, has been deduced from its cDNA. Amid regions homologous to other Mg-dependent phosphatases, a 200- residue, highly acidic insertion was found, which contained a motif similar to the Ca-binding repeat of calnexin and motifs for casein kinase II (confirmed by in vitro phosphorylation). Nuclear function of the enzyme is implicated by a nuclear entry signal and a bi-partite nuclear localization domain near the C-terminus. Northern analyses further revealed that the phosphatase is present in all animals and in all tissues examined.